We are seeking support to obtain and operate for three years a Mark II-A analyzer--an automated, high-resolution system for the quantitative determination of the ultraviolet-absorbing constituents of urine. This system prototype was developed by Oak Ridge National Laboratory under contracts from NIH. It is comprised of a heated, high-pressure anion- exchange column for the separation step and a continuous-flow ultraviolet spectrophotometer for the detection step. Separation is achieved by elution with an acetate buffer of gradually increasing concentration. The total analysis time is plus or minus 24 hours. Chromatograms showing the absorbance of the column effluent as a function of time are recorded by a strip-chart recorder and by a data acquisition system containing a digital voltmeter and paper tape punch. The output from the latter is then used as the input to a digital computer for analysis of the chromatogram. More than 143 chromatographic peaks have been resolved from a 2-ml sample. Normal urine samples yield similar chromatograms. We would utilize this instrument for an in-depth study of a heredofamilial disease, Charcot- Marie-Tooth syndrome. This would include a systematic component characterization of profile peaks suggesting abnormalities when compared to controls, including the absence of normal components. For such determinations, paper chromatography, paper electrophoresis, and ultraviolet spectrophotometry would be routinely used. As necessitated by the individual compound, additional methods would be employed, including mass spectroscopy, nuclear magnetic resonance, and infrared spectrometry. The Mark II-A would be concurrently utilized on a cooperative, cost-sharing basis by the Crippled Children's Division for genetic studies of retardation and the Clinical Research Center for cancer patient screening.